Updated Results Show Ongoing Treatment-Free Remission in CML Trial

About half of patients with chronic myeloid leukemia in chronic phase (CML-CP) who stopped therapy with second-line nilotinib remained in treatment-free remission (TFR) about 3.7 years after stopping, according to updated results of the ENESTop trial (abstract 7005) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.

“Late molecular relapse was rare, with only one patient having lost response since the 2.8-year analysis,” said Francois-Xavier Mahon, MD, PhD, of the University of Bordeaux in France. “These findings suggest that switching to second-line nilotinib may enable more patients to reach TFR eligibility and to achieve successful TFR.”

ENESTop is one of three trials currently evaluating TFR after nilotinib in this patient population. According to Mahon, TFR in CML-CP offers patients relief from any treatment-related side effects, reduced risk of toxicity from long-term treatment, and improved quality of life.

In the trial, patients were previously treated with imatinib before switching to nilotinib (imatinib for > 4 weeks, then nilotinib for ≥ 2 years). Patients who achieved molecular response (MR^4.5) on nilotinib continued on the drug in a 52-week consolidation phase (163 patients) to be sure response was maintained. Patients who maintained response (77%) were eligible for the TFR phase of the study.

At the meeting, Mahon presented data evaluating maintenance of response from a follow-up period of 192 weeks. At data cutoff, 56 of 126 (46.0%) patients were still in TFR. The median duration of TFR was 139.3 weeks.

The treatment-free survival rate at 192 weeks was 50.5% (95% CI, 41.2%–58.7%). Of the 61 patients who were in TFR at the 2.8-year evaluation, only 1 patient lost response by 3.7 years, 1 patient discontinued because of a serious adverse event, and 1 discontinued because of patient/guardian decision.

“Stopping treatment was safe because we are able to re-induce molecular response,” Mahon said.

Fifty-nine of 126 patients lost TFR and entered a re-initiation phase. The majority of these patients regained either MR⁴ (94.9%) or MR^4.5 (93.2%).

There were no deaths attributable to CML and no new deaths occurred since the 2.8-year analysis. Five patients died; one during the consolidation phase, two during the TFR phase, and two more than 30 days after discontinuing treatment in the re-initiation phase. 

The overall adverse event burden tended to decrease during TFR, with musculoskeletal pain–related adverse events resolving over time, Mahon said.

Abstract discussant Jacqueline S. Garcia, MD, of Dana-Farber Cancer Institute in Boston, called the updated data from ENESTop impressive, as it showed that durable TFR is possible after stopping second-line nilotinib for those previously achieving sustained MR. She did note though that the trial had a high bar for entry into the TFR phase.

“With a number of treatment discontinuation studies showing success in just about half the patients that attempt it, we need to require even longer data readout to see how this impacts long-term survival and curability,” Garcia said. “This study puts us one step closer to the concept of TFR, this being the closest we might be able to get to a non-transplant cure.”